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Disease-modifying effects of TMEM106B in genetic frontotemporal dementia: a longitudinal GENFI study
Saira Saeed Mirza, Maurice M. Pasternak, Andrew D. Paterson, Ekaterina A. Rogaeva, Maria Carmela Tartaglia, Sara Berman Mitchell, Sandra E. Black, Morris Freedman et al.. Brain, 2025-04-22
Topic: Brain proteins, microglia and lab models
Common variants within TMEM106B are associated with risk for frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). C9orf72: rs1990622G allele dosage was associated with less atrophy within the right occipital region in presymptomatic carriers at baseline, and reduced atrophy rate within putamen and caudate nucleus, right frontotemporal regions, left cingulate and bilateral insular cortices in symptomatic carriers over time; lower NfL levels in presymptomatic carriers at baseline; better executive functions and language abilities in presymptomatic carriers; and maintained overall cognitive functions and behaviour in symptomatic carriers over time. GRN: rs1990622G allele dosage was associated with reduced grey matter atrophy rate within the right temporal and occipital regions in presymptomatic carriers, and within the right frontal cortex and insula over time in symptomatic carriers; lower serum NfL levels over time in presymptomatic carriers and lower NfL levels at both baseline and over time in symptomatic carriers; and better global cognitive performance at baseline and higher attention/processing speed scores over time in symptomatic carriers. MAPT: rs1990622G allele dosage was associated with reduced grey matter atrophy rate within the right inferior frontal gyrus in symptomatic carriers, but no effects on serum NfL or cognitive/behavioural measures.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Mirza, S. S., Pasternak, M. M., Paterson, A. D., Rogaeva, E. A., Tartaglia, M. C., Mitchell, S. B., et al. (2025). Disease-modifying effects of TMEM106B in genetic frontotemporal dementia: a longitudinal GENFI study. Brain. https://doi.org/10.1093/brain/awaf019
Vancouver
Mirza SS, Pasternak MM, Paterson AD, Rogaeva EA, Tartaglia MC, Mitchell SB, et al. Disease-modifying effects of TMEM106B in genetic frontotemporal dementia: a longitudinal GENFI study. Brain. 2025. doi:10.1093/brain/awaf019. PMID: 40260680.
BibTeX
@article{mirza2025-40260680,
author = {Mirza, Saira Saeed and Pasternak, Maurice M. and Paterson, Andrew D. and Rogaeva, Ekaterina A. and Tartaglia, Maria Carmela and Mitchell, Sara Berman and Black, Sandra E. and Freedman, Morris and others},
title = {{Disease-modifying effects of TMEM106B in genetic frontotemporal dementia: a longitudinal GENFI study}},
journal = {Brain},
year = {2025},
doi = {10.1093/brain/awaf019},
pmid = {40260680},
url = {https://doi.org/10.1093/brain/awaf019}
}
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Key findings
- Common variants within TMEM106B are associated with risk for frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP).
- C9orf72: rs1990622G allele dosage was associated with less atrophy within the right occipital region in presymptomatic carriers at baseline, and reduced atrophy rate within putamen and caudate nucleus, right frontotemporal regions, left cingulate and bilateral insular cortices in symptomatic carriers over time; lower NfL levels in presymptomatic carriers at baseline; better executive functions and language abilities in presymptomatic carriers; and maintained overall cognitive functions and behaviour in symptomatic carriers over time.
- GRN: rs1990622G allele dosage was associated with reduced grey matter atrophy rate within the right temporal and occipital regions in presymptomatic carriers, and within the right frontal cortex and insula over time in symptomatic carriers; lower serum NfL levels over time in presymptomatic carriers and lower NfL levels at both baseline and over time in symptomatic carriers; and better global cognitive performance at baseline and higher attention/processing speed scores over time in symptomatic carriers.
- MAPT: rs1990622G allele dosage was associated with reduced grey matter atrophy rate within the right inferior frontal gyrus in symptomatic carriers, but no effects on serum NfL or cognitive/behavioural measures.
Why it matters
In a longitudinal study of genetic frontotemporal dementia, a common TMEM106B variant was linked to less brain atrophy, lower NfL levels, and better cognitive and behavioral measures in carriers of C9orf72 and GRN mutations, with limited effects in MAPT carriers. This suggests TMEM106B may modify disease course, but it is an observational finding, not a treatment.
Study details
- Study designcohort study
- Participants518
- Effect size58.1%
- Evidence strengthModerate
How this study scored 63/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 518 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 7 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 7 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Sergi Borrego‐Écija: h-index 28 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Centre National de la Recherche Scientifique: institution h-index 2,511 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 59 institution(s) in 10 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40260680) |
| Free to read | 2 / 2 | Free to read |
| Total | 63 / 100 | — |
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